We plan to investigate the temporal and quantitative relationships between immune effector and immunoregulatory responses to the 13762 mammary adenocarcinoma in the syngeneic Fischer rat. We have previously demonstrated that after intraperitoneal injection of 10 to the 7th power tumor cells, animals develop both T-lymphocyte mediated cytotoxicity (CMC) and humoral factors blocking CMC in vitro. Soluble tumor antigen and antibody to tumor antigen in the blood increase exponentially until death. Suppressor cells begin to accumulate in the spleen after day 7, increasing in concentration until death. Blocking factors, cytotoxic cells and suppressor cells are all specific for the tumor cell. Detailed analysis shows that 7 days after inoculation immune serum contains three factors blocking CMC: tumor antigen, antigen-anti-tumor antibody complexes, and an IgG-blocking factor (IgG-BF) which binds to immune lymphocytes but not to tumor cells. Similarly specific immunoglobulins appear after immunization with immune spleen cells from tumor-bearing animals. Furthermore, ascites tumor inocula contain as much as 14% host lymphocytes; when tumor inocular are treated with anti-lymphocyte serum and complement, the IgG-BF does not appear and animal survival is prolonged. These are characteristics of an anti-receptor antibody for lymphocyte receptors for tumor antigen. This study proposes to develop the necessary reagents (radiolabeled, purified soluble tumor antigen, antibody to tumor antigen and IgG-BF (the putative anti-receptor antibody)), to investigate the conditions inducing and maintaining regulatory components, particularly the relationship between tumor antigen load and the level of regulatory components. Also, it proposes to examine whether anti-receptor antibodies and/or suppressor cells are involved in cycling of the cytolytic lymphocyte response to the tumor, and, ultimately, on the basis of an understanding of auto-regulation, to develop methods of specific immunotherapy against the tumor.